Dasatinib potentially a new SOC for children with CML-CP

Of the 33 patients on PFOS, 22 eventually switched to tablet formulation.

Results

The primary endpoint for imatinib-R/I patients—MCyR greater than 30%—was reached by 3 months, and MCyR at 12 and 24 months exceeded 90%. The median time to response was 3.1 months (range, 2.8 – 4.1), and median duration of response was not yet reached (range, 54.9 – not estimable).

For newly diagnosed patients, the preset defined rate of interest of 55% for CCyR was reached as early as 6 months, and exceeded 90% by 12 and 24 months.

Dr Gore pointed out that intolerant patients also reached CCyR relatively quickly, although it was not a specified endpoint.

Data indicate that responses occurred relatively quickly and continued to increase over time of follow-up.

MMR also continued to increase over time and showed no difference between formulation and response rate.

Median PFS has not been reached, as only 7 patients in each cohort had disease progression.

One imatinib-R/I patient died 1 year after stopping treatment. The patient, who had a GI bleed unrelated to dasatinib, had discontinued therapy for progressive disease with loss of MCyR.

Safety

Overall safety was very similar to the dasatinib exposure and experience in adults, Dr Gore said, and there were no differences in events between PFOS and tablets.

One patient in the PFOS cohort had a dasatinib-related grade 3 hypersensitivity reaction, which resolved after discontinuation of dasatinib.

“What’s important here,” she said, “is that there were almost no adverse events of severity in either cohort, only 1 in the imatinib refractory and intolerant and 1 in the newly diagnosed cohorts.”

“Most importantly for those of us with a lot of experience in this field,” she added, “there were no occurrences of pleural effusion, pericardial effusion, pulmonary edema, pulmonary hypertension, or any vascular occlusive events in patients noted on this trial.”

“Additionally, for pediatricians, we care a lot about what happens to growth in these patients and prospectively we collected a lot of data related to growth parameters in bone growth and development."

Of the dasatinib-related adverse events occurring in 10% or more of patients, there were only 5 growth and development events noted out of the 113 patients treated and all were grade 1 or 2 events, Dr Gore pointed out.

In the R/I cohort, one patient had osteopenia and gynecomastia. At the time of data analysis, this event had resolved even though the patient continued on dasatinib.

“We believe our data suggests that dasatinib could be considered as a new standard of care for children with CML in chronic phase,” she said.

“It includes the advantage of a liquid formulation as well as the advantages of once daily dosing and administration without regard to fed or fasting state,” she added, “which for all of us who treat children know could be quite important.”

The study was funded by Bristol-Myers Squibb.